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Genetic biomarkers for hepatocellular cancer risk in a caucasian population

World Journal of Gastroenterology 2017年第36期23卷 6674-6684页

作者： Elena De Mattia Erika Cecchin Jerry Polesel Alessia Bignucolo Rossana Roncato francesco lupo Marina Crovatto Angela Buonadonna Claudio Tiribelli Giuseppe Toffoli Clinical and Experimental Phar-macology “Centro di Riferimento Oncologico”-National Cancer Institute Unit of Cancer Epidemiology “Centro di Riferimento Oncologico”-National Cancer Institute General Surgery 2U and Liver Transplantation Center A.O.U.Cittàdella Salute e della Scienza di TorinoUniversity of Torino Cytogenetics and Molecular Biology Unit Santa Maria degli Angeli Hospital Pordenone Medical Oncology Unit “Centro di Riferimento Oncologico”-National Cancer Institute Fondazione Italiana Fegato AREA Science Park

AIM To uncover novel genetic markers that could contribute to predicting hepatocellular carcinoma(HCC)susceptibility in Caucasians. METHODS The present retrospective case-control study compared genotype frequencies between a cohort of HCC cases and two,independent,HCC-free,age/sex-matched control *** HCC cohort comprised 192 homogeneous patients that had undergone orthotopic liver *** first control group comprised167 patients that were matched to the HCC cohort for the percentage of hepatitis B(HBV)and/or hepatitis C(HCV)infections.A second control group included192 virus-free,healthy individuals that were used to evaluate the generalizability of the identified predictive *** cases and controls were *** three study populations were characterized with a panel of 31 markers derived from 21 genes that encoded key proteins involved in hepatocarcinogenesis-related *** study end-point was to assess the association between genetic variants and HCC onset. RESULTS Five genetic markers were identified as risk factors for HCC in high-risk patients infected with HBV/*** to a dominant model,reduced HCC risk was associated with three polymorphisms:ERCC1rs3212986(OR=0.46,95%CI:0.30-0.71,P=0.0005),GST-P1 rs1138272(OR=0.41,95%CI:0.21-0.81,P=0.0097),and CYP17A1 rs743572(OR=0.50,95%CI:0.31-0.79,P=0.0032).Conversely,according to a recessive model,increased HCC risk was associated with two polymorphisms:XRCC3 rs1799794(OR=3.70,95%CI:1.02-13.39,P=0.0461)and ABCB1 rs1128503(OR=2.06,95%CI:1.18-3.61,P=0.0111).These associations remained significant in a subgroup analysis,where patients were stratified according to viral status(HBV-or HCV-positive serology).Two variants exhibited a serology-specific effect:ABCB1 rs1128503(OR=4.18,95%CI:1.55-11.29,P=0.0048)showed an effect in the HBV-positive subgroup;and ERCC1 rs3212986(OR=0.33,95%CI:0.18-0.60,P=0.0003)showed an effect in the HCV-positive *** the five markers identified,E

关键词： ERCC1 XRCC3 GST-P1 CYP17A1 MDR-1 Polymorphisms Hepatocellular carcinoma risk Early diagnosis Antiviral therapy Hepatitis B viral/hepatitis C viral

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